Figure illustrates the rapid lower limb colloid transit lost under conditions of spinal anesthesia and minimal accumulation of colloid in the inguinal lymph nodes.
This study sought to determine the influence of spinal anesthesia and associated sympathectomy on lower limb lymphatic flow—a previously unstudied area of research. The observation of a reduction in lymphatic flow of radioisotope-labeled colloid from the injection site in all analyzed limbs demonstrated proof-of-concept.
The likely mechanism for our observations is the loss of normal sympathetically mediated peristaltic lymphangion contraction—the predominant means of lymph flow propulsion at rest.7 The sympathectomy, induced by spinal anesthesia, reduced the efferent outflow from the thoracic sympathetic chain at levels T9-L1 (the sympathetic supply to lower limbs).6 The observation of blood pressure and heart rate reduction in all patients (and dermatome block higher than T9) was used as an indicator of sympathetic blockade. Our findings reflect those of animal studies where sympathetic stimulation accelerated lymph flow and sympathetic blockade abolished lymph flow.8
Our observations have implications for future research into the perioperative behavior of lymphatics during cancer surgery. Induced, temporary sympathectomy to the tumor microenvironment of residual disease may be of therapeutic advantage given the role of neural adrenergic nervous system in stimulating lymphangiogenesis,1 lymph channel dilation, and tumor growth.9 Furthermore, surgical inflammation increases lymph flow, with passive opening of lymphatic pores to limit tissue edema and assist clearance of perilymphatic cellular debris.10 Detached (isolated) tumor cells from the surgical site are cleared by lymphatic systems. Plausibly, a reduction in perioperative lymphatic flow and isolated tumor cell release from the surgical site through the use of spinal anesthesia may confer oncological benefit.
Given the unexpected magnitude of effect in this exploratory study, the demonstration of proof-of-concept and the acknowledged inconvenience, and considerable discomfort for patients in study participation, the study was terminated prematurely. A limitation of the study remains the small sample size. Because of variability in lymph flow, and to minimize confounding, the study design ensured patients acted as their own biological controls: lymph flow was compared before/after spinal anesthesia specific to the same limb. The coadministered intrathecal clonidine could conceivably affect lymphatic flow, although this effect would have been uniform across all patients. Although lymphoscintigraphy commenced >60 minutes after the administration of sympathomimetics, these agents are a potential confounder, although their influence would manifest as a reduction in the observed effect.
We report proof-of-concept for spinal anesthesia achieving a reduction in lymphatic flow. In addition to contributing a novel understanding of the physiologic, neural regulation of lymphatic flow in humans, the results may have implications for the provision of anesthesia for cancer resection surgery, sentinel node biopsy, and the lymphedema of complex regional pain syndrome. The clinical relevance of our findings to impact cancer recurrence patterns requires further study.
We thank the following for their valuable contribution to the conceptualization and conduct of the study: Mr. Mark Scalzo, Professor Rod Hicks, Dr. David Bernshaw, Dr. Beauregard Jean-Mathieu, Mr. Peter Eu (colloid preparation).
Name: Jonathan G. Hiller, MBBS (Hons.), GCEpi, FANZCA.
Contribution: Protocol development, ethics application and study registration, study funding, manuscript preparation.
Name: Hilmy M. Ismail, MD, FRCA, FFARCS(I), FANZCA.
Contribution: Concept and protocol development, ethics application, study funding, study conduct, manuscript preparation.
Name: Michael S. Hofman, MBBS (Hons), FRACP, FAANMS.
Contribution: Protocol development (colloid dosimetry), study funding, imaging, and preparation of results.
Name: Kailash Narayan, MBBS, MD, PhD, FRANZCR.
Contribution: Protocol development.
Name: Shakher Ramdave, MBBS, MD, FRACP, FAANMS.
Contribution: Protocol development (colloid dosimetry), ethics application.
Name: Bernhard J. Riedel, MD, FRCA, FANZCA, MBA, PhD.
Contribution: Study funding, manuscript preparation.
This manuscript was handled by: Honorio T. Benzon, MD.
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